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H J Issaq

Publications and source records attributed to H J Issaq.

72 records · Page 4Linked to original sources
PubMed1987

Inflammatory, proliferative, and neoplastic lesions at the site of metallic identification ear tags in Wistar [Crl:(WI)BR] rats.

During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcomas) was diagnosed in 168 rats. Histologically, almost 90% of the rats in this study (henceforth referred to as Study I) showed some significant lesion at the tag site including various degrees of chronic inflammation, chondrous hyperplasia, and osseous metaplasia of the pinnal cartilage. In marked contrast, only two tumors were detected in 193 animals in a second study (Study II) in the same strain of rats, and only 56% of the rats had lesions at the tag site. A high incidence (greater than 25%) of clinically severe inflammation at the tag site was seen early in Study I and persisted during the first 6 mo of the study, while the incidence of such reactions in Study II was never more than 1%. Elemental analysis of the tags provided no explanation for the differences between the two studies, as tags used in both studies were of the same composition, predominantly nickel and copper. Metallic internal prostheses have induced local malignancies in humans and animals, and the present observations provide further evidence of the hazard posed by such devices at the site of prolonged contact with tissues. These findings suggest that a persistent tissue reaction may be an important factor in tumor development.

Alloys↗
PubMed1984

Separation of polychlorinated biphenyls (Aroclor 1254) by high-performance liquid chromatography.

The separation of Aroclor 1254 on various reversed-phase columns was investigated. The results show that the cyano- and phenyl-bonded columns performed poorly, but C18 bonded columns gave better results. It was also found that the absorption wavelength at which the effluent is monitored has great effect on the detection of these isomers. The optimum conditions for the separation and detection are: C18, 5 micron; reversed-phase column, 20 cm X 4.6 mm I.D.; acetonitrile-water (60-40); flow-rate 1.5 ml/min; detection at 210 nm or 205 nm.

Aroclors↗
PubMed1984

Lymphokines inhibit macrophage RNA synthesis.

The effects of lymphokine (LK) preparations on the incorporation of [3H]uridine into macrophage RNA were investigated. Supernatants from murine spleen cells activated in vitro by alloantigens or Con A, and shown to contain macrophage-activating factor (MAF), were used as the source of LK. It was observed that such LK preparations contain factor(s) causing a profound inhibition of [3H]uridine incorporation into the RNA of proteose-peptone-elicited peritoneal macrophages. Such RNA-labeling inhibitory factor (RIF) was absent in control supernatants from nonstimulated cultures, and showed activation curves similar to that of MAF. RIF activity was not due to altered permeability of macrophages to [3H]uridine nor to the changes in the specific activity of the pool of RNA precursors, but rather reflected an altered metabolism of RNA. The inhibition of RNA synthesis was dependent upon the presence of nanogram amounts of LPS as a costimulator. Moreover, the response to RIF appeared to be genetically controlled since macrophages from C3H/HeJ mice were not affected by RIF, while C3H/HeN mice were fully responsive. In parallel cultures of macrophages, LK were also tested for their MAF activity, and a strong similarity between the biological conditions in which MAF and RIF activities were expressed could be demonstrated. The assay for RIF provides a new and convenient parameter for measuring macrophage-sensitive LK activity that might be very useful for monitoring purification or for screening of T-cell hybridoma supernatants.

Animals↗
PubMed1983

RNA synthesis in activated macrophages I. Poly(I) X poly(C)-induced triggering of cytolytic activity is associated with decrease in RNA synthesis.

The effects of polyinosinic, polycytidylic acid [poly(I) X poly(C)] on the activation and RNA metabolism in murine peritoneal macrophages (M phi) elicited by proteose-peptone (pM phi) was investigated. Poly(I) X poly(C) triggered the cytolytic activity of pM phi and augmented their glucose oxidation. In contrast, a profound depression of [3H]uridine incorporation into RNA was observed in poly(I) X poly(C)-activated pM phi. The degree of depression of RNA labeling paralleled the dose of poly(I) X poly(C) used to activate the pM phi and the expression of tumoricidal activity. This decrease in [3H]uridine incorporation into M phi RNA could not be accounted for by decreased permeability of the activated M phi to [3H]uridine, or by instability of the labeled RNA. Moreover, analysis of the specific activity of the intracellular uridine triphosphate (UTP) pool and studies on the labeling of M phi RNA with [32P] orthophosphate indicated that the decreased RNA labeling was not due to changes in the specific activity of UTP. We concluded that poly(I) X poly(C)-activated pM phi exhibit a depressed rate of RNA synthesis. We suggest that the rate of RNA synthesis may be investigated as a potential new indicator for M phi activation.

Animals↗
PubMed1982

Synthesis of primary bile acids by rat liver epithelial cell-lines.

Several lipid metabolites were identified in liver epithelial cell-lines established from different strains of rats, using high performances liquid chromatographic techniques. [14C]-acetate was shown to be incorporated by these cultured cells into cholesterol, 7 alpha-hydroxycholesterol and the primary bile acids. Labeled cholesterol was localized in the cells whereas cholic and chenodeoxycholic acids were found in the culture medium as conjugates of taurine and glycine. These conjugated primary bile acids were also detected in the extracts of culture medium, after separating them using reverse phase thin layer chromatography. Therefore, the cultured rat liver cells retain the liver-specific property of synthesizing bile acids, even after they become cell-lines.

Acetates↗
PubMed1977

Nondestructive distinction between aflatoxin B1 and ethoxyquin in thin-layer chromatography.

A rapid and simple method has been developed for the nondestructive distinction between aflatoxin B1 and the feed antioxidant, ethoxyquin. These two chemicals exhibit similar RF values in certain solvent systems and produce a similar bluish fluorescence under long UV (366 nm) radiation. The method involves the in situ generation of fluorescence spectra of the respective thin-layer chromatography spots. Since it is nondestructive, the method affords ancillary study of the separated aflatoxins.

Aflatoxins↗
PubMed1977

Detection reagent for adenine, guanine, uracil, cytosine and their alkylated bases, nucleotides and nucleosides on thin-layer plates.

The detection of alkylated bases at the nanogram level is reported. The reaction is based on two steps, first, chlorination of the bases and, secondly, spraying the chlorinated product with o-tolidine solution to give a dark blue color. The detection of nucleotides and nucleosides is also possible. The optimum conditions and the possible mechanism of the reaction are discussed.

Adenine↗
PubMed1977

Separation of alkylated guanines, adenines, uracils and cytosines by thin-layer chromatography.

A one-dimensional thin-layer chromatographic (TLC) method using a mixture of two solvents and commercially available silica gel plates to separate mixtures of alkylated guanines, adenines, uracils and cytosines is presented. RF values for the bases and the solvent systems used are listed. The addition of approximately 1 ml of ammonium hydroxide to the solvent has been found to prevent streaking and results in non-distorted developed spots. A mixture of 19 adenine and uracil bases was resolved on silica gel plates employing two-dimensional TLC. Chloroform-methanol (90:10) was used for the first dimension and chloroform-propanol (90:30) for the second.

Adenine↗
PubMedDate not supplied

Promotion of mouse lung tumors by bioaccumulated polychlorinated aromatic hydrocarbons.

Lung tumors initiated in infant Swiss mice by N-nitrosodimethylamine (NDMA) were promoted by a single dose of a mixture of polychlorinated biphenyls (PCBs), Aroclor 1254 (250 or 500 mg/kg) given 4 days later. The tumors were typical alveologenic adenomas, and their number increased gradually over the course of 1 year to a maximum 4-fold enhancement in average tumor number compared with those given NDMA alone. The time course pattern suggested continuous tumor stimulation by the nonmetabolized PCB congeners retained in the tissues. Content of the nine major bioretained PCB congeners in carcass, liver, and lung was determined at intervals after treatment. Several showed tissue-specific retention patterns: 2,3,3',4,4'-PCB was selectively retained in lung and liver, and 2,2',3,4,4', 5'-HCB in lung. In tests of the tumor-promoting ability of individual congeners, the 2,2',3,4,4',5'-HCB, an Ah receptor agonist, promoted lung tumors when given singly, whereas another prominent bioretained congener, the 2,2',4,4',5,5'-HCB, an Ah receptor antagonist, did not promote, and in fact abrogated the positive effect of the 2,2',3,4,4',5'-HCB. In a parallel examination of persistent biochemical effects, a single low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (5 nmole/kg) resulted in significant elevation of immunochemically detected protein and enzymatic activity of cytochrome P450 IA1 in lung for at least 12 weeks; these parameters were elevated for at least 30 weeks after a single dose of Aroclor 1254 (500 mg/kg). Taken together these results suggest that Ah-receptor-dependent induction of cytochrome P450 IA1 in mouse lung is correlated with and possibly causally involved in promotion of tumors by retained congeners.

Animals↗
PubMedDate not supplied

Debrisoquine metabolism and lung cancer risk.

Previous reports of the association between the debrisoquine metabolic polymorphism and lung cancer risk have been conflicting. We examined the hypothesis that the genetically determined ability to metabolize debrisoquine identifies individuals at increased risk for lung cancer in a study designed to address some of the methodological criticisms of previous studies. A case-control study of 335 incident Caucasian lung cancer patients and 373 controls matched for age, race, sex, and hospital, was conducted at the National Naval Medical Center (Bethesda, MD) and at the Laval Hospital (Sainte-Foy, Quebec, Canada). Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8-h urine collected. Stratified and logistic regression analyses were used to evaluate the association between extensive or intermediate debrisoquine metabolism and lung cancer risk. We found no increased risk among extensive or intermediate metabolizers (odds ratio, 0.6; 95% confidence interval, 0.3-1.2). The lack of an association was not confounded by control diagnoses, medications used within 1 month of debrisoquine administration, smoking, stage, or histology of lung cancer. No relationship was found among either heavy smokers or light and nonsmokers. Our results do not support the role of debrisoquine metabolism as a marker for lung cancer risk. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, debrisoquine metabolic phenotype was not associated with lung cancer risk in these data.

Aged↗
PubMedDate not supplied

Selective retention of polychlorinated biphenyl congeners in lung and liver after single-dose exposure of infant mice to Aroclor 1254.

Infant male Swiss mice (8 days old) were given a single i.p. injection of 500 mg/kg of the polychlorinated biphenyl (PCB) mixture, Aroclor 1254, a treatment found in previous studies to result in promotion of nitrosamine-initiated lung and liver tumors. The amounts of the nine congeners that account for > 90% of the PCBs still present 1 day after treatment were quantified in liver, lung, and remainder of carcass 1, 7, 56, 84, and 112 days after treatment. Rates of decrease (half-times, dt1/2s) for total PCB concentration and for individual congeners were compared within and between compartments and with body weight doubling time. In carcass (adipose compartment) there was net loss beyond that expected from dilution due to growth, with the predicted lower dt1/2s for the more metabolizable congeners. By contrast, in lung, after a rapid loss during the 1st week, all congeners except for #153 (2,2'4,4'5,5'-hexachlorobiphenyl [HCB]) were retained and decreased in amount only as a function of dilution due to growth. One result was that congeners #105 (2,3,3',4,4'-pentachlorobiphenyl [PeCB]) and #138 (2,2',3,4,4',5'-HCB) constituted a higher proportion in lung than in carcass. A complex pattern was observed in liver: relative to carcass, there was retention of all congeners during the prepubertal growth phase, again with specific enrichment of #105, followed by more rapid depletion of certain congeners later. PCB-binding proteins and changes in lipid composition may contribute to these phenomena, which are of human relevance in that these congeners are commonly found in human serum and adipose samples.

Animals↗